2009年8月19日,，北京生命科學研究所高紹榮實驗室在Biology of Reproduction雜志在線發(fā)表題為“The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development”的文章,，報道了組蛋白去甲基化酶JMJD2C在小鼠早期胚胎中的特異性表達及其在胚胎發(fā)育過程中的作用。
DNA甲基化與組蛋白修飾等表觀遺傳修飾在胚胎發(fā)育過程中起重要作用,。盡管近幾年研究發(fā)現核心組蛋白甲基化修飾具有可逆性,，并發(fā)現組蛋白去甲基化酶JMJD2C可以通過調節(jié)轉錄因子NANOG的表達來調控小鼠ES細胞的多能性，但是關于這一新發(fā)現的組蛋白去甲基化酶在胚胎發(fā)育過程中的作用仍不清楚,。該文章發(fā)現JMJD2C在小鼠早期胚胎發(fā)育過程中的表達具有時期特異性：從2-細胞期開始表達,，在4-細胞期達到最高水平，并逐漸下降持續(xù)到囊胚期,。該文章通過注射Jmjd2c特異的dsRNA到小鼠MII卵子中并孤雌活化,，下調Jmjd2c mRNA表達水平，發(fā)現胚胎發(fā)育大部分停滯在囊胚期之前。mRNA及蛋白表達檢測結果表明下調Jmjd2c mRNA表達水平可顯著引起Nanog,，Pou5f1和Sox2這些多能性基因,，以及Myc和Klf4這些與細胞增殖相關基因的表達下調。這一結果表明胚胎早期發(fā)育停滯可能是這些基因表達變化的協(xié)同作用結果,。該文章首次在證明JMJD2C不僅對ES細胞全能性具有調節(jié)作用,，在小鼠胚胎早期發(fā)育中也具有重要作用。
王瑊玏(中科院動物研究所聯(lián)合培養(yǎng)博士生)為本文的第一作者,；參與此項工作的還有張苗(博士生),，張郁(技術員)，寇朝輝(技術員)和中科院動物所的韓之明和孫青原研究員,。北京生命科學研究所的高紹榮博士和中科院動物研究所的陳大元研究員為本文的共同通訊作者,。該研究由科技部和北京市科委資助，在北京生命科學研究所完成,。（生物谷Bioon.com）
生物谷推薦原始出處：
Biology of Reproduction August 19, 2009, doi: 10.1095/?biolreprod.109.078055
The Histone Demethylase JMJD2C Is Stage-Specifically Expressed in Preimplantation Mouse Embryos and Is Required for Embryonic Development
Jianle Wang, Miao Zhang, Yu Zhang, Zhaohui Kou, Zhiming Han, Da-Yuan Chen, Qing-Yuan Sun and Shaorong Gao
Epigenetic modifications play a pivotal role in embryonic development by dynamically regulating DNA methylation and chromatin modifications. Although recent studies have shown that core histone methylation is reversible, very few studies have investigated the functions of the newly discovered histone demethylases during embryonic development. In the present study, we investigated the expression characteristics and function of JMJD2C, a histone demethylase that belongs to the JmjC-domain-containing histone demethylases, during preimplantation embryonic development of the mouse. We found that JMJD2C is stage-specifically expressed during preimplantation development, with the highest activity being observed from the two-cell to the eight-cell stage. Depletion of JMJD2C in metaphase II oocytes followed by parthenogenetic activation causes a developmental arrest before the blastocyst stage. Moreover, consistent with a previous finding in embryonic stem (ES) cells, depletion of JMJD2C causes a significant down-regulation of the pluripotency gene Nanog in embryos. However, contrary to a previous report in ES cells, we observed that other pluripotency genes, Pou5f1 and Sox2, are also significantly down-regulated in JMJD2C-depleted embryos. Furthermore, the depletion of JMJD2C in early embryos also caused significant down-regulation of the Myc and Klf4 genes, which are associated with cell proliferation. Our data suggest that the deregulation of these critical genes synergistically causes the developmental defects observed in JMJD2C-depleted embryos.
